PROJECT SUMMARY Proteios is an emerging startup driven to reduce the rising cost of healthcare. Prescription drug costs are the fastest rising component and are contributing to the dramatic increase in healthcare costs. The worldwide focus of pharmacy and biotechnology is now in two areas: 1) biopharmaceutical development and production and 2) cell therapies. Cell therapies have demonstrated enormous promise for transforming the treatment of cancer and other debilitating diseases, and the FDA has already approved their use for the treatment of leukemia and lymphoma. However, some cell therapies cost over $350,000 per treatment, which has made these life-saving technologies inaccessible to many patients. The objective of this proposal is to show feasibility of a simple and effective method for cell enrichment and cell depletion commonly used during cell therapy. Our short-term goal for Phase I of the SBIR award is to validate that we can enrich T lymphocytes as starting material for CAR T cell manufacturing using a novel, antibody-free isolation platform based on proprietary protein technology and nucleic acid aptamers by immunoaffinity capture of cells that express the Cluster of Differentiation (CD) marker protein CD4. The platform will use a silica-binding peptide covalently linked to a nucleic acid aptamer that recognizes a cell surface protein of interest. The resulting peptide-aptamer chimera will reversibly bind cells to silica, an abundant, non-toxic, and inexpensive material. Our approach avoids challenging and costly steps where antibodies or other proteins are covalently modified to bind to beads or small molecules. Additionally, our approach eliminates commonly used reagents that cause oxidative damage to cells. When commercialized, this approach will alleviate some of the concerns with current technologies - such as high cost, long development times, lack of automation, and complicated, multistep chemistry. The development of products for cell isolation using the Proteios platform has the potential to reduce the cost of cell enrichments more than tenfold. Furthermore, this technology could transform the production process for therapeutic cells to make life-saving cell therapies available to more individuals.